DESCRIPTION: (Applicant's Abstract) This proposal outlines a clinician-scientist training program in molecular biology, which includes didactic course work and laboratory investigation. It will be conducted under the supervision of an experienced mentor in a supportive research environment with the ultimate goal of transitioning the applicant to an independent physician/research. The broad objective of the applicant is to better understand the molecular basis of retinal development, particularly retinal ganglion cell determination and differentiation. The ultimate goal is to assimilate this information into an integrated understanding of retinal development that may advance future transplantation and/or regeneration therapies for retinal and optic nerve disease. The proposed research plan endeavors to develop an inducible system for retinal ganglion cell specific expression in order to further characterize retinal transcription factors and their networks in vivo with the use of microarray analysis. The initial specific aim of the project is to develop a doxycycline mediated system for in vivo retinal ganglion cell specific gene expression in transgenic mice. This system permits the control of both the timing and dosage of gene expression by the administration of doxycycline in drinking water. The second specific aim is to use this system to induce the expression of the POU domain containing retinal ganglion cell development as evidenced by a 70% reduction in retinal ganglion cell number in Brn3b knockout mice. The final specific aim is to ascertain the network of genes regulated by Brn3b using microarrays. Microarray analysis, which offers an opportunity to identify and quantify the simultaneous expression of a large number of genes, is well suited for the identification of those genes that are up-regulated or down-regulated by a particular transcription factor under various conditions.